弥漫性大B细胞淋巴瘤基因变异特征与18F-FDG PET/CT SUVmax的关系解析及其临床意义

田田, 陈晨, 魏然, 包龙龙, 顾丙新, 张群岭, 曹军宁, 于宝华, 李小秋, 周晓燕

  1. 1.复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，复旦大学病理研究所，上海 200032
    2.复旦大学附属肿瘤医院核医学科，复旦大学上海医学院肿瘤学系，上海 200032
    3.复旦大学附属肿瘤医院肿瘤内科，复旦大学上海医学院肿瘤学系，上海 200032
  • 收稿日期:2025-02-20 修回日期:2025-03-26 出版日期:2025-06-30 发布日期:2025-07-14
  • 通信作者: 周晓燕（ORCID: 0000-0001-5999-7237），主任医师，教授。
  • 作者简介:田田（ORCID:0000-0003-3112-3735），博士，住院医师。
  • 基金资助:
    上海市协同创新集群(2019CXJQ03);上海市科学技术委员会“ 科技创新行动计划”医学创新研究专项(20Z11900300)

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摘要/Abstract

摘要：

背景与目的： 弥漫性大B细胞淋巴瘤（diffuse large B cell lymphoma，DLBCL）分子遗传学特征和患者治疗前18F-FDG PET/CT检查评估的SUVmax值均与患者预后密切相关，但两者的关系及其与R-CHOP治疗方案治疗反应的相关性尚不清楚。本研究旨在分析DLBCL分子遗传学特征与治疗前经18F-FDG PET/CT检测的SUVmax值的关系及其与临床病理学特征、R-CHOP治疗反应的相关性。方法： 回顾性收集复旦大学附属肿瘤医院2022—2023年同时经淋巴瘤481基因DNA panel二代测序（next-generation sequencing，NGS）和治疗前经PET/CT检查的DLBCL患者225例，本研究通过复旦大学附属肿瘤医院医学伦理委员会的审查（伦理批号：050432-4-2307E）并获得患者知情同意；除基因突变特征外，同时收集荧光原位杂交法检测的BCL2、BCL6和MYC基因易位情况；另收集该组病例的临床病理学参数以及经R-CHOP治疗后的PET/CT检查结果。结果： 总计191例DLBCL患者纳入最终分析，重要基因MYD88突变、TP53突变、CDKN2A/2B拷贝数异常、CD79B突变发生率分别为24.6%、27.2%、32.5%和16.8%。治疗前SUVmax值范围是5.10~63.10（24.44±10.70，中位22.80）。MYD88L265P突变型DLBCL的治疗前SUVmax值显著高于MYD88野生型DLBCL（P=0.039），SUVmax值与DLBCL其他基因变异类型包括TP53突变、CDKN2A/B拷贝数减少、CD79B突变、KMT2D突变、TNFAIP3突变、B2M突变、EZH2突变、BTG1/2突变、CREBBP突变、MYC、BCL2、BCL6基因重排之间无显著的相关性。治疗前高SUVmax值与高血清乳酸脱氢酶（lactate dehydrogenase，LDH）水平（P=0.012）及非生发中心（non-germinal center B-cell-like，non-GCB）亚型显著相关（P=0.040），但与R-CHOP治疗反应无显著的相关性（P=0.714）。DLBCL中TP53基因突变与R-CHOP治疗反应差显著相关（P=0.001），是R-CHOP治疗后非完全代谢缓解的独立预测因子。联合TP53基因突变、Ann Arbor分期、国际预后指数（International Prognostic Index，IPI）及血清LDH水平能够更好地预测患者对R-CHOP治疗的反应。结论： 在DLBCL中，MYD88L265P突变型患者具有较高的治疗前SUVmax值。DLBCL治疗前SUVmax值与R-CHOP治疗反应无关，而TP53基因突变与R-CHOP治疗反应差显著相关，并且是独立预测因子。TP53基因突变联合临床病理学参数可更好地预测R-CHOP治疗反应。关于各基因变异特征及SUVmax值与患者预后的关系尚需作进一步随访研究。

关键词: 弥漫性大B细胞淋巴瘤, 基因变异特征, 18F-FDG PET/CT, SUVmax, R-CHOP, 治疗反应

Abstract:

Background and purpose: Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma (DLBCL) and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients’ prognosis. However, their relationship and the associations with R-CHOP response of DLBCL are still unclear. This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL. Methods: A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected. This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (Ethical No.: 050432-4-2307E) and acquired the informed consent of the patients. The translocations of BCL2, BCL6 and MYC were identified by fluorescence in situ hybridization. The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected. Results: Finally, 191 patients were enrolled in this study. The frequency of MYD88 mutation, TP53 mutation, copy number variations of CDKN2A/2B, CD79B mutation in the 191 DLBCL patients were 24.6%, 27.2%, 32.5% and 16.8%, respectively. The range of baseline SUVmax was 5.10-63.10 (24.44±10.70, median 22.80). The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type (P=0.039). There were no significant associations of SUVmax with other gene alterations including TP53 mutation, CDKN2A/B loss, CD79B mutation, KMT2D mutation, TNFAIP3 mutation, B2M mutation, EZH2 mutation, BTG1/2 mutation, CREBBP mutation, gene translocations of MYC, BCL2 and BCL6. The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase (LDH) level (P=0.012) and non-germinal center B-cell-like (non-GCB) DLBCL (P=0.040). However, there was no significant association of SUVmax with R-CHOP response (P=0.714). TP53 mutation was significantly associated with the poor response of R-CHOP (P=0.001) and was an independent predictor of non-complete metabolic response (non-CMR). TP53 mutation combined with Ann Arbor stage, International Prognostic Index (IPI) score and serum LDH level could better predict R-CHOP response than each factor alone. Conclusion: MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax. The baseline SUVmax was not associated with R-CHOP response. However, TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients. TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response. The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

Key words: Diffuse large B cell lymphoma, Genetic alterations, 18F-FDG PET/CT, SUVmax, R-CHOP, Therapeutic response

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